OTULL_HUMAN
ID OTULL_HUMAN Reviewed; 356 AA.
AC Q9NUU6; Q53H50; Q9H037;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Inactive ubiquitin thioesterase OTULINL;
GN Name=OTULINL {ECO:0000303|PubMed:31056421, ECO:0000312|HGNC:HGNC:25629};
GN Synonyms=FAM105A {ECO:0000303|PubMed:31056421,
GN ECO:0000312|HGNC:HGNC:25629};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 239-356.
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP LACK OF ACTIVITY.
RX PubMed=23708998; DOI=10.1038/nature12296;
RA Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A.,
RA Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y.,
RA Raught B., Gingras A.C., Sicheri F., Cordes S.P.;
RT "The linear ubiquitin-specific deubiquitinase gumby regulates
RT angiogenesis.";
RL Nature 498:318-324(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 87-356, FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, LACK OF ACTIVITY, DOMAIN, AND MUTAGENESIS OF
RP 2-ALA--LYS-83; ASP-139 AND HIS-352.
RX PubMed=31056421; DOI=10.1016/j.str.2019.03.022;
RA Ceccarelli D.F., Ivantsiv S., Mullin A.A., Coyaud E., Manczyk N.,
RA Maisonneuve P., Kurinov I., Zhao L., Go C., Gingras A.C., Raught B.,
RA Cordes S., Sicheri F.;
RT "FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes
RT to the ER Membrane.";
RL Structure 0:0-0(2019).
CC -!- FUNCTION: Lacks deubiquitinase activity. {ECO:0000269|PubMed:31056421}.
CC -!- SUBUNIT: Does not bind ubiquitin or ubiquitin-like proteins.
CC {ECO:0000269|PubMed:31056421}.
CC -!- INTERACTION:
CC Q9NUU6; Q13520: AQP6; NbExp=3; IntAct=EBI-6916492, EBI-13059134;
CC Q9NUU6; Q6ZVE7: GOLT1A; NbExp=3; IntAct=EBI-6916492, EBI-17231387;
CC Q9NUU6; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-6916492, EBI-1052304;
CC Q9NUU6; O43464: HTRA2; NbExp=3; IntAct=EBI-6916492, EBI-517086;
CC Q9NUU6; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-6916492, EBI-10266796;
CC Q9NUU6; O14901: KLF11; NbExp=3; IntAct=EBI-6916492, EBI-948266;
CC Q9NUU6; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-6916492, EBI-10192441;
CC Q9NUU6; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-6916492, EBI-10262251;
CC Q9NUU6; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-6916492, EBI-8638294;
CC Q9NUU6; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-6916492, EBI-2548832;
CC Q9NUU6; Q9Y320: TMX2; NbExp=3; IntAct=EBI-6916492, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31056421}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:31056421};
CC Peripheral membrane protein {ECO:0000269|PubMed:31056421}. Nucleus
CC envelope {ECO:0000269|PubMed:31056421}.
CC -!- DOMAIN: The N-terminal region that precedes the OTU domain mediates
CC interaction with cellular membranes. {ECO:0000269|PubMed:31056421}.
CC -!- SIMILARITY: Belongs to the peptidase C65 family. Otulin subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Although highly similar to the deubiquitinase OTULIN, lacks
CC the conserved active site Cys at position 139 which is replaced by an
CC Asp residue, and does not show deubiquitinase activity.
CC {ECO:0000269|PubMed:31056421, ECO:0000305|PubMed:23708998}.
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DR EMBL; AK001989; BAA92023.1; -; mRNA.
DR EMBL; AK222731; BAD96451.1; -; mRNA.
DR EMBL; BC011524; AAH11524.1; -; mRNA.
DR EMBL; AL512750; CAC21673.1; -; mRNA.
DR CCDS; CCDS3884.1; -.
DR RefSeq; NP_061891.1; NM_019018.2.
DR PDB; 6DRM; X-ray; 2.06 A; A=87-356.
DR PDBsum; 6DRM; -.
DR AlphaFoldDB; Q9NUU6; -.
DR SMR; Q9NUU6; -.
DR BioGRID; 119988; 407.
DR IntAct; Q9NUU6; 12.
DR STRING; 9606.ENSP00000274217; -.
DR iPTMnet; Q9NUU6; -.
DR PhosphoSitePlus; Q9NUU6; -.
DR BioMuta; FAM105A; -.
DR DMDM; 74734394; -.
DR EPD; Q9NUU6; -.
DR jPOST; Q9NUU6; -.
DR MassIVE; Q9NUU6; -.
DR MaxQB; Q9NUU6; -.
DR PaxDb; Q9NUU6; -.
DR PeptideAtlas; Q9NUU6; -.
DR PRIDE; Q9NUU6; -.
DR ProteomicsDB; 82720; -.
DR Antibodypedia; 22546; 131 antibodies from 21 providers.
DR DNASU; 54491; -.
DR Ensembl; ENST00000274217.4; ENSP00000274217.3; ENSG00000145569.6.
DR GeneID; 54491; -.
DR KEGG; hsa:54491; -.
DR MANE-Select; ENST00000274217.4; ENSP00000274217.3; NM_019018.3; NP_061891.1.
DR UCSC; uc003jfj.4; human.
DR CTD; 54491; -.
DR DisGeNET; 54491; -.
DR GeneCards; OTULINL; -.
DR HGNC; HGNC:25629; OTULINL.
DR HPA; ENSG00000145569; Tissue enhanced (bone).
DR neXtProt; NX_Q9NUU6; -.
DR OpenTargets; ENSG00000145569; -.
DR PharmGKB; PA142671788; -.
DR VEuPathDB; HostDB:ENSG00000145569; -.
DR eggNOG; ENOG502QVY0; Eukaryota.
DR GeneTree; ENSGT00390000009802; -.
DR HOGENOM; CLU_051856_0_0_1; -.
DR InParanoid; Q9NUU6; -.
DR OMA; GKLRKCI; -.
DR OrthoDB; 1416236at2759; -.
DR PhylomeDB; Q9NUU6; -.
DR TreeFam; TF328709; -.
DR PathwayCommons; Q9NUU6; -.
DR SignaLink; Q9NUU6; -.
DR BioGRID-ORCS; 54491; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; FAM105A; human.
DR GenomeRNAi; 54491; -.
DR Pharos; Q9NUU6; Tbio.
DR PRO; PR:Q9NUU6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9NUU6; protein.
DR Bgee; ENSG00000145569; Expressed in monocyte and 142 other tissues.
DR Genevisible; Q9NUU6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR InterPro; IPR023235; FAM105.
DR InterPro; IPR023236; OTULINL.
DR PANTHER; PTHR33662; PTHR33662; 1.
DR Pfam; PF16218; Peptidase_C101; 1.
DR PRINTS; PR02055; PROTEINF105.
DR PRINTS; PR02056; PROTEINF105A.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Membrane; Nucleus;
KW Reference proteome.
FT CHAIN 1..356
FT /note="Inactive ubiquitin thioesterase OTULINL"
FT /id="PRO_0000274404"
FT DOMAIN 128..356
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT REGION 1..83
FT /note="Required for membrane binding"
FT /evidence="ECO:0000269|PubMed:31056421"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 319
FT /note="F -> L (in dbSNP:rs16903574)"
FT /id="VAR_030281"
FT MUTAGEN 2..83
FT /note="Missing: Loss of membrane binding."
FT /evidence="ECO:0000269|PubMed:31056421"
FT MUTAGEN 139
FT /note="D->C: Fails to confer catalytic activity; when
FT associated with N-352."
FT /evidence="ECO:0000269|PubMed:31056421"
FT MUTAGEN 352
FT /note="H->N: Fails to confer catalytic activity; when
FT associated with C-139."
FT /evidence="ECO:0000269|PubMed:31056421"
FT CONFLICT 322
FT /note="N -> I (in Ref. 2; BAD96451)"
FT /evidence="ECO:0000305"
FT HELIX 96..103
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 109..125
FT /evidence="ECO:0007829|PDB:6DRM"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 167..174
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 195..214
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 233..259
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 280..286
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:6DRM"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:6DRM"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:6DRM"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:6DRM"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:6DRM"
FT STRAND 340..349
FT /evidence="ECO:0007829|PDB:6DRM"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:6DRM"
SQ SEQUENCE 356 AA; 42196 MW; 91EEC6C877D5315B CRC64;
MAATRSPTRA RERERSGAPA AGSDQVHSWM LATSQALDTV WRMAKGFVML AVSFLVAAIC
YFRRLHLYSG HKLKWWIGYL QRKFKRNLSV EAEVDLLSYC AREWKGETPR NKLMRKAYEE
LFWRHHIKCV RQVRRDNYDA LRSVLFQIFS QGISFPSWMK EKDIVKLPEK LLFSQGCNWI
QQYSFGPEKY TGSNVFGKLR KYVELLKTQW TEFNGIRDYH KRGSMCNTLF SDAILEYKLY
EALKFIMLYQ VTEVYEQMKT KKVIPSLFRL LFSRETSSDP LSFMMNHLNS VGDTCGLEQI
DMFILGYSLE VKIKVFRLFK FNSRDFEVCY PEEPLRDWPE ISLLTENDRH YHIPVF
